August 23, 1996
Researchers find gene involved in colon cancer; learn why some cells become malignant
TORONTO - A husband and wife research team at The Hospital for Sick Children has discovered a gene implicated in the development of colon cancer - a disease from which approximately 6,000 Canadians will die this year.
Drs. Liliana Attisano and Jeff Wrana's discovery has brought cancer researchers a step closer in understanding what causes cells to multiply uncontrollably - an activity which leads to the development of malignancies. Their research is reported in the August 23 issue of Cell.
The gene, called MADR2, is located on chromosome 18 in a section that is also involved in the development of other human malignancies, such as pancreatic cancer. MADR2 produces a protein important for conducting signals that govern cell growth. When MADR2 is functioning normally it acts as a tumor suppressor. However, a defective MADR2 gene prevents cells from receiving the growth regulating signal.
"A key step in the development of malignancies is the cell's loss of sensitivity to a molecule called Transforming Growth Factor b (TGFb)," explains Dr. Attisano, an assistant professor of Anatomy and Cell Biology at the University of Toronto and a member of the Division of Gastroenterology and Nutrition in the Research Institute at The Hospital for Sick Children. "TGFb negatively regulates cell growth. A mutated MADR2 gene prevents the cell from receiving the TGFb signal, so it keeps growing. This can lead to the development of tumors."
Gaining an understanding of the events which cause a loss of sensitivity to TGFb could provide important insights into the general mechanisms underlying the causes of malignancies.
"With this new discovery of MADR2 in the TGFb signal pathway, work can begin on developing possible methods of gene therapy to replace the defective gene," explains Dr. Wrana, an assistant professor of Anatomy and Cell Biology at the University of Toronto and a member of the Division of Gastroenterology and Nutrition in the Research Institute of The Hospital for Sick Children. "It's possible that a new class of drugs could be created which would mimic the function of the protein, overcoming the defective gene."
The Canadian Cancer Society estimates that 16,300 Canadians will be diagnosed with colon cancer this year. Of those, 8,800 will be men and 7,500 will be women. The Society also estimates that 6,200 Canadians will die from the disease this year.
Collaborators in this work include researchers Drs. Lap-Chee Tsui and Stephen W. Scherer at The Hospital for Sick Children; Steven Gallinger and Irene L. Andrulis at The Samuel Lunenfeld Research Institute at Mount Sinai Hospital; Gerald H. Thomsen at the Institute for Cell and Developmental Biology at the State University of New York and the University of Toronto.
This research was supported by the Medical Research Council of Canada, The National Cancer Institute of Canada, the Canadian Breast Cancer Research initiative, the Canadian Genetic Diseases Network, the Howard Hughes International Fellowship, the U.S. National Science Foundation and the American Heart Association.
Infrastructure costs of the Research Institute are supported by The Hospital for Sick Children Foundation.
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